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Applications of Functional Near-Infrared Spectroscopy(fNIRS) to Neurorehabilitation of Cognitive Disabilities

First Published on: 25 October 2006To link to this article: DOI: 10.1080/13854040600878785URL: http://dx.doi.org/10.1080/13854040600878785

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APPLICATIONS OF FUNCTIONAL NEAR-INFRAREDSPECTROSCOPY (fNIRS) TO NEUROREHABILITATIONOF COGNITIVE DISABILITIES

Patricia M. Arenth1, Joseph H. Ricker1, andMaria T. Schultheis2

1Department of Physical Medicine & Rehabilitation and the Center for theNeural Basis of Cognition, University of Pittsburgh, PA, and 2Department ofPsychology and School of Biomedical Engineering, Drexel University,Philadelphia, PA, USA

Functional Near-Infrared Spectroscopy (fNIRS) is a neuroimaging technique that utilizes

light in the near-infrared spectrum (between 700 and 1000 nm) to detect hemodynamic

changes within the cortex when sensory, motor, or cognitive activation occurs. FNIRS prin-

ciples have been used to study brain oxygenation for several decades, but have more recently

been applied to study cognitive processes. This paper provides a description of basic fNIRS

techniques, and provides a review of the rehabilitation-related literature. The authors dis-

cuss strengths and weaknesses of this technique, assert that fNIRS may be particularly ben-

eficial to neurorehabilitation of cognitive disabilities, and suggest future applications.

INTRODUCTION AND GOALS

The aim of this paper is to describe a neuroimaging technique that appears tohold unique promise for utilization within the area of neurorehabilitation. This tech-nique, functional Near-Infrared Spectroscopy (fNIRS), relies on optical techniquesto detect changes in the hemodynamic response within the cortex when sensory,motor, or cognitive activation occurs. While optical techniques (i.e., those that arederived from the physical principles of light absorption and reflectance) have beenapplied to the study of brain oxygenation and metabolism for several decades (Hill& Keynes, 1949; Jobsis, 1977), the earnest use of fNIRS to study cognitive processesand neurorehabilitation began only within the last 10 to 15 years. In the followingsections we aim to provide a description of this novel technique, a review of therehabilitation-related fNIRS studies that have been published up to this point,and a discussion of strengths and limitations of this method. In addition, we hope

Address correspondence to: Patricia M. Arenth, PhD, University of Pittsburgh, Department of

Physical Medicine & Rehabilitation, Kaufmann Building, Suite 202, 3471 Fifth Avenue, Pittsburgh, PA

15213, USA. E-mail: [email protected] or [email protected]

# 2006 Taylor & Francis Group, LLC, an informa business

The Clinical Neuropsychologist, 21: 38–57, 2007

http://www.psypress.com/tcn

ISSN: 1385-4046 print=1744-4144 online

DOI: 10.1080/13854040600878785

Accepted for publication: June 19, 2006. First published online October 25, 2006.

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to suggest ways in which fNIRS may be particularly applicable to some of the uniqueresearch problems associated with neurorehabilitation.

DESCRIPTION OF FUNCTIONAL NEAR-INFRARED SPECTROSCOPY (fNIRS)

fNIRS detects brain responses in a manner similar to that of PET and fMRI.That is, increases in metabolic demand as a consequence of cognitive activation leadsto the well-known hemodynamic response, which ultimately increases total bloodflow, regional blood volume, and regional blood oxygenation (Roy & Sherrington,1890). The imaging data acquired in fMRI are achieved through recording of theblood oxygen level dependent (BOLD) signal, which relies on differences in the mag-netic properties of oxyhemoglobin (oxy-Hb) and deoxyhemoglobin (deoxy-Hb).

Like fMRI, fNIRS also depends on the ratio of oxy-Hb and deoxy-Hb, but theoptical properties—rather than paramagnetic properties—of this ratio are the focusof concern: Oxy-Hb and deoxy-Hb are the primary light-absorbing constituents inthe brain, and each absorbs near-infrared light in a different manner. To capturedata regarding changes in the oxy-Hb and deoxy-Hb ratio, the fNIRS procedureinvolves the placement of light sources and detectors on the scalp. Near infrared light(defined as non-ionizing electromagnetic radiation with wavelengths between 700and 1000 nm) is projected through the scalp and skull, and ultimately penetrates intothe first several millimeters of brain tissue. An array of photodiode detectors recordsthe wavelengths of light reflected and absorbed.

The basic brain-dedicated fNIRS instrumentation is composed of threemodules: a simple headpiece that holds the fNIRS emitters and sensors, the dataacquisition board which hosts the electronic system to control the light sourcesand collect the reflected light, and the host server (Danen, Wang, Thayer, & Yodh,1998) (see Figure 1).

This fairly simple and relatively inexpensive method allows for the quantifi-cation of changes in oxy-Hb and deoxy-Hb and, by summation, total blood volume(total-Hb) that are related to changes in brain activity during motor or cognitivetasks (Villringer & Chance, 1997). In addition, because fNIRS data is processed inthe same manner as fMRI data and, as in fMRI , these outputs can be used to gen-erate brain maps of activation, direct comparison between the two methods is poss-ible through the use of standard brain-mapping software such as SPM or othersimilar programs.

Although investigational, in addition to measuring some of the same physio-logical parameters as conventional brain-imaging procedures, fNIRS possessesseveral potential advantages over these techniques that are particularly relevant torehabilitation applications. For example, within the rehabilitation population, it isnot unusual for individuals to have a history of multiple exposures to ionizing radi-ation associated with x-ray or other imaging procedures due to complicated and oftenlong-term issues related to injury or illness. As near-infrared light sources are non-ionizing and do not exceed the energy accumulated by the brain on a sunny day, theyare not harmful to tissue and repeated monitoring via fNIRS is considered to be safe.FNIRS procedures are non-invasive and are safe for use with individuals who haveplates, pins, or other metallic implants that might preclude the use of magnetic ima-ging techniques, such as fMRI. As such medical hardware is not at all uncommon for

FUNCTIONAL NIRS AND NEUROREHABILITATION 39

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individuals in the rehabilitation population, the use of fNIRS may provide an opport-unity to safely study individuals who may otherwise be ineligible to be evaluated usingother methods. In addition, when compared to the large, expensive equipment anddedicated space needed for other imaging techniques, the ‘‘simplicity’’ of the equip-ment required for fNIRS allows it to be less expensive and ultimately more usablefor more frequent and repeated studies of the same subject.

The size and configuration of this equipment also make it potentially possibleto conduct fNIRS in an office setting, at bedside, in therapy, or even potentially in ahome setting, making this method more convenient and less intimidating for thepatients or subjects, and decreasing the likelihood that they would experience theclaustrophobic or fearful reactions often associated with fMRI.

With the potential portability of systems and the lack of sensitivity tomovement during data acquisition, perhaps the greatest advantage of all is theability to use fNIRS equipment in ‘‘real-life’’ situations. As the true purpose ofrehabilitation is to assist individuals in the return to the highest possible levels offunctional independence, the opportunity to monitor brain activity while individualsare engaged in actual functional activities may prove to be an invaluable resource forguiding therapeutic treatments and measuring or even predicting the brain’sresponse in the context of progress towards goals. This technique, therefore, hasthe potential to significantly impact standards of care and eventual outcomes for

Figure 1 The basic brain-dedicated fNIRS instrumentation.

40 PATRICIA M. ARENTH ET AL.

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individuals who are engaging in rehabilitation following significantly disabilitatinginjuries or illness.

Despite the advantages suggested above, it should be noted that there are cur-rently some limitations and needs for further development of this technique. Forexample, to date there has not been consistency in the development of fNIRS probesor instrumentation, and there has been significant variability in the measurements(i.e., oxy-Hb, deoxy-Hb, total Hb) and methods reported in the literature. As a result,there is a need for increased standardization in order to establish the reliability and val-idity of fNIRS. In addition there are also limitations in spatial resolution (limited toapproximately 1 inch depth), which may make fNRS inappropriate for studying somebrain regions or types of function, thus limiting its applicability to some degree. Whilefull descriptions of the various types of instrumentation and design are beyond thescope of this paper, it is important to consider these issues as the current literature isdiscussed, and as the development of fNIRS techniques moves forward. Through thefollowing review of the literature, we hope to provide information about the work thathas been done up to this point, and to fuel additional discussion about the strengths andlimitations of this technique, as well as potential future directions for study.

fNIRS RESEARCH

fNIRS has been in used in various research and industrial contexts for severaldecades, however its utilization in research on cognitive processes and neurorehabil-itation has been a very recent development. Prior to the 1990s, most fNIRS studieshad been of neonates. In the early 1990s, Villringer and colleagues (Villringer,Planck, Hock, Schleinkofer, & Dirnagl, 1993) introduced fNIRS as a ‘‘new tool’’for studying hemodynamic changes in the brain during cognitive activity. Throughtheir study of 16 healthy adult subjects participating in visual stimulation and pictureobservation tasks, they found a pattern of increases in oxy-Hb and correspondingdecreases in deoxy-Hb associated with cognitive activity. They were able to demon-strate that these changes were not due to alterations in skin blood flow, but ratherdue to hemodynamic changes in the brain. They asserted that this technique couldbe developed into a viable bedside method for collecting data regarding cerebralhemodynamics related to brain activity. Similar conclusions were drawn by simul-taneous investigations by Chance and colleagues (i.e., Chance, 1991; Chance,Zhwang, Lipton, Alter & Rachofsky, 1992). These initial studies served to demon-strate the potential assets offered by fNIRS and provided an initial framework forfuture studies, that to date have covered a variety of behaviors.

Motor and Visual Tasks

Perhaps due to a need to establish baseline studies of cortical applications offNIRS technology in the literature, several studies have focused on observationsof areas of the brain where the localization of function has been more established,such as in visual and motor regions of cortex. For example, in motor studies, acommon finding regarding hemodynamic response during finger opposition taskshas been an increase in oxy-Hb and a decrease in deoxy-Hb, with greatest changesnoted in the sensorimotor cortex, contralateral to the hand performing the task


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(i.e., Francescini, Fantini, Thompson, Culver, & Boas, 2003; Maki, Yamashite,Yoshitoshi, Watanabe, Mayanagi, & Koizumi, 1995; Obrig et al., 1996; Watanabe,Yamashita, Maki, Ito, & Koizumi, 1996). These findings have generally beenconsistent with previous fMRI findings (i.e., Allison, Meador, Loring, Figueroa,& Wright, 2000; Cramer, Finkelstein, Schaechter, Bush, & Rosen, 1999).

Additional common findings have focused on the differences in timing ofchanges in oxy-Hb and deoxy-Hb, with increases in oxy-Hb occurring prior todecreases in deoxy-Hb in the contrateral motor cortex following performance of ahand opening=closing task (Jadzewski, Strangman, Wagner, Kwong, Poldrack, &Boas, 2003) and a seqential finger opposition task (Obrig et al., 1996).

fNIRS studies of motor tasks have also demonstrated more detailed basic acti-vation patterns in gait: For example, Miyai and colleagues (2001) found bilaterallyincreased levels of oxy-Hb and total Hb in the medial primary sensorimotor corticesand supplementary motor areas with walking activity. When subjects were asked toengage in alternating foot movement without actual walking, activation fell into asimilar pattern, but was reduced. When an alternating arm swing (as if walking)was performed without gait, oxy-Hb increases were noted only in the lateral portionof the primary sensorimotor regions. In comparison, when subjects were asked toimagine walking without doing so, activation was noted caudally in the bilateralsupplementary motor areas. Two of eight subjects then completed the imageryand alternating foot movements during fMRI. The activation patterns were foundto be consistent between fNIRS and fMRI for these two tasks. The general findingswere consistent with the previous work mapping motor movement, however fNIRSallowed for greater description due to the ability to study active movement.

In an additional fNIRS study of active versus passive motor movement,Francescini and colleagues (2003) compared the strength and patterns of activationfor a finger opposition task (active movement) and a passive tactile stimulation con-dition as well as a condition in which electrical stimulation was applied to the hand.Their findings regarding patterns of activation were consistent with previous PETand fMRI findings (i.e., an increase in oxy-Hb and decrease in deoxy-Hb in the sen-sorimotor cortex contralateral to the stimulated hand). They also found strongerhemodynamic response to be associated with the active voluntary task (finger oppo-sition) as compared to the passive tactile and electrical stimulation conditions. In anadditional study, which will be described later in this paper, Okamoto and colleagues(2004) also found differences in activation associated with performance of actual ver-sus ‘‘mock’’ performance of motor tasks. Differences such as these may speak to thelimitations of studying functional activities while utilizing methods such as fMRI,which significantly limit movement during imaging, and suggest that fNIRS maybe a more useful technique for studying the cortical hemodynamics associated withactive motor function.

Similar to findings of studies utilizing motor-related paradigms, evaluations ofhemodynamic response in the occipital cortex following visual stimulation have alsoshown patterns indicating an increase in oxy-Hb mirrored by a decrease of deoxy-Hb(Heekeren et al., 1997; Jasdzweski et al., 2003; Kato, Kamei, Takashima, & Ozaki,1993; Obrig et al., 2002). Despite such similarities, some differences in the timing ofmotor and visual hemodynamic response have been noted. For example, Jasdzweskiand colleagues (2003) found that while visual data were qualitatively similar to motor


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data, there was some difference in the initial pattern of the oxy-HB and deoxy-HBratio change, as well as a simultaneous peak for oxy-Hb, deoxy-HB, and total Hb.This finding was consistent with the findings of other visual cortex studies, but variedfrom response in the motor cortex. The authors suggested that such differences maybe due to different capillary transit times within the motor and visual cortices.

Visual studies have also been used to attempt to evaluate whether a linearrelationship exists between neuronal and hemodynamic activity in the brain uponvisual stimulation (Gratton, Goodman-Wood, & Fabiani, 2001; Obrig et al., 2002;Wolf et al., 2003). Findings of these studies have generally supported the model ofsuch a relationship within the visual cortex. Additional fNIRS studies using a visualparadigms have shown localization of function to the visual cortex, consistent withother types of neuroimaging results (Meek et al., 1995). Two other fNIRS visual stu-dies of note found differences in activation using various levels of stimulus intensity(Wolf et al., 2003), and evidence of decreased hemodynamic response followinghabituation using a visual paradigm (Obrig et al., 2002).

Cognition

Initial studies applying fNIRS for assessing different types of cognitive abilityoften included less standardized tasks. For example, Chance, Zhuang, UnAh, Alter,and Lipton (1993) measured changes in cerebral hemodynamics associated with sub-jects’ performance of visually presented abstract thinking tasks. Hoshi and Tamura(1993) studied subjects during visual and auditory stimulation, as well as during conduc-tion of mental tasks, such as mentally solving a mathematical problem. That same year,Hoshi and Tamura (1993) also found differences in hemodynamic response between anolder and younger group of subjects performing a mental problem-solving task, andOkada, Tokumitsu, Hoshi, and Tamura (1993) observed gender and handedness differ-ences in hemodynamic response in subjects completing a mirror drawing task.

From the late 1990s through to the present, there has been an increase in thenumber of fNIRS studies related to higher-level cognitive functioning. In their 2003review article, Obrig and Villringer suggested, however, that there is a gap in the litera-ture between studies of basic functions, such as the motor and visual studies notedabove, and the complexity of such functions as language and higher-level cognitivetasks. Not surprisingly, as compared to the studies of motor and visual functioning,fNIRS findings of higher-level cognitive functions are more complex and varied, withless consistency in patterns of oxy-Hb and deoxy-Hb reported. In fact, as previouslysuggested, some of the greatest limiting factors in our ability to establish the reliabilityand validity of fNIRS, and to discuss trends in the literature, are the variability of thefunctions studied, the methods used, and the measurements reported.

fNIRS studies of language provide an example of these challenges: Languageparadigms have included comparisons of semantic anomalies versus a regularreading task (Horovitz & Gore, 2004), syntactic versus semantic decision tasks(Noguchi, Takeuchi, & Sakai, 2002), and performance by aphasic versus non-aphasic subjects (Sakatani, Yuxiao, Lichty, Li, & Zuo, 1998). While in each of thesestudies, differences in localization of hemodynamic response were evident whenwithin-study paradigm tasks were compared, the variability between language tasksacross studies and variations in protocols limits direct comparison.


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As an additional example, Cannestra and colleagues (Cannestra, Watenburge,Obrig, Villringer, & Toga, 2003) conducted a localization study of language func-tioning using fNIRS. They assessed hemodynamics related to covert visual objectnaming versus motor movement of the tongue and hand (right finger opposition).Using an fNIRS system with light-emitting optodes located over the precentral sul-cus and light-detecting optodes placed both 3 cm anterior (over the prefrontal cortex)and 3 cm posterior (over the pericentral region), they were able to distinguish Broca’sarea from motor areas. The overall findings were therefore consistent with what isknown about cortical areas associated with language and motor functioning. How-ever, they also found an overlap in oxy-Hb changes, with increases noted in bothanterior and posterior optode positions across all tasks for all subjects. In contrast,changes in deoxy-Hb were more pronounced, more localized and varied in locationwith each task. For example, deoxy-HB decreases were noted during both motortasks in the posterior position, with no significant deoxy-Hb change in the anteriorposition noted during a finger opposition task, while deoxy-Hb decreases were notedin the anterior position during a tongue movement task, but at a lower magnitude ascompared to the posterior. In comparison, during the covert visual naming task,oxy-Hb increases were noted in both the anterior and posterior positions, with great-er significance in the anterior position. Decreases in deoxy-Hb were noted only in theanterior position, with increases in deoxy-HB actually noted in the posteriorposition. Based on these findings, the authors concluded that deoxy-Hb may bethe best parameter for mapping language cortices using fNIRS.

Statements of Obrig and Villringer (2003) were in agreement with Cannastraand colleagues. They noted that, based on the physiological basis of the BOLD sig-nal, a decrease in deoxy-Hb is indeed the most valid parameter indicating cortical‘‘activation.’’ They also point out, however, that that one of the problems in thefNIRS literature, is that oxy-Hb changes are often used as the parameter of choice,and deoxy-Hb changes are only sometimes reported. Unfortunately, this is case inseveral other language studies (e.g., Kennan, Horovitz, Maki, Yamashita, Koizumi,& Gore, 2002; Noguchi et al., 2002; Saki, Hashimoto, & Homae, 2001), makingdirect comparison in the fNIRS language literature additionally complicated.

Comparison of other studies of higher-level cognitive processes pose similarchallenges. As an example, Fallgatter and Strick conducted two separate studies uti-lizing fNIRS with differents tasks associated with frontal lobe functioning. In 1997,the authors observed hemodynamic patterns during subject performance of theContinuous Performance Test (CPT). Their findings indicated primarily right frontalactivation. Statistically, they observed significant differences between hemispherichemodynamics, with significant differences noted in deoxy-Hb during task perform-ance as compared to baseline, but no significant changes in oxy-Hb in the right, ascompared to the left hemisphere. In a 1998 study by these same authors, healthysubjects performed the Wisconsin Card Sorting Test during fNIRS. Compared tobaseline at rest, findings indicated a significant oxy-Hb increase bilaterally in thefrontal brain regions.

Studies focusing on the prefrontal cortex have also yielded varying results:For example, in a study of 14 healthy subjects, Schroeter and colleagues (Schroeter,Zysset, Kupka, Kruggel, & von Cramon, 2002) utilized an event-related design in whichfNIRS was used to measure changes in oxy-hemoglobin, deoxy-hemoglobin, total


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hemoglobin, and the redox state of cytochrome-c-oxidase (Cyt-Ox) in 14 healthy sub-jects completing a color–word matching Stroop task. They found patterns of increasedoxy-Hb and total Hb, and decreased deoxy-Hb concentrations indicating brain acti-vation patterns similar to what has been observed in other studies. Stronger hemody-namic response was noted in the lateral prefrontal cortex bilaterally for incongruentas compared to neutral or congruent trials, suggesting that the interference duringthe incongruent trials induced stronger brain activation. The authors concluded thatit is feasible to use an event-related design in fNIRS studies of cognition.

Another study of prefrontal cortex functioning conducted by Toichi andcolleagues (2004) used fNIRS to investigate changes in hemodynamic response forsimple attention versus higher cognitive processing tasks with 10 Japanese and 10American healthy adult subjects. Results of this study found increases in oxy-HBand decreases in deoxy-HB in the prefrontal cortex during higher-level cognitivetasks (both verbal and visual), with increases in tissue hemoglobin saturation(THS) noted as well. In comparison, increases in both oxy-HB and deoxy-HB wereobserved during basic attention tasks, with no significant changes in THS noted. Thepatterns of hemodynamic response were found not to be affected by either task dif-ficulty or language. The authors suggested that differing patterns in changes indeoxy-Hb might be a distinguishing marker in studying prefrontal cortex activationduring attention versus higher-level cognitive tasks.

In addition to the studies mentioned above, in recent years, Dr. Britton Chanceand his colleagues at the University of Pennsylvania have spearheaded developmentand testing of fNIRS technology for other cognitive applications. The collaborationof the applicant team of biomedical engineers from Drexel University with Dr.Chance has focused on functional optical brain imaging as a means to assess cogni-tive workload during attention and working memory tasks as well as complex taskssuch as war games performed by healthy volunteers under operational conditions(Izzetoglu, Bunce, Izzetoglu, Onaral, & Pourrezaei, 2003; Izzetoglu, Bunce, Onoral,Pourrezaei, & Chance, 2004).

While, overall, fNIRS studies of cognitive functioning have found activationin brain regions that are generally consistent with fMRI and other brain-mappingtechniques, the variability of results reported in the literature needs to be evaluatedfurther. It is possible that further validation of fNIRS techniques on more basicfunctions may assist in the application of fNIRS to more complex functions. Inaddition, the development of consistent instrumentation, methods, and measurementreporting will be important for establishment of reliability and validity to occur.

Aging and Psychiatric Populations

While most earlier baseline studies utilized healthy subject groups, morerecently studies of groups with psychiatric or neurological diagnoses have also begunto appear. For example, Fallgatter and Strik (1997) used fNIRS to study elderlyhealthy controls in comparison to subjects with probable Dementia of the Alzhei-mer’s Type (DAT) during performance of verbal fluency tasks (both letter and cate-gory). While both groups performed better on the category task, healthy subjectsperformed significantly better on both tasks, as compared to subjects with DAT.In addition, reduced baseline oxygenation was noted for DAT subjects. During


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performance of the verbal fluency tasks, an expected oxy-HB increase was noted inthe left hemisphere for controls, as compared to the right hemisphere. A loss ofhemispheric lateralization was noted for DAT subjects. Other fNIRS studies havealso shown evidence of a decrease in hemodynamic response associated with Alzhei-mer’s disease (Hock et al., 1996; Hock et al., 1997) and normal aging (Hock, Muller-Spahn, Schuh-Hofer, Hofmann, Dirnagle, & Villringer, 1995; Hock et al., 1996;Hoshi & Tamura, 1993; Kwee & Nakada, 2003; Mehagnoul-Schipper et al., 2002;Schroeter, Zysset, Kruggel, & von Cramon, 2003). Decreases in activation withinregions of interest and alterations in hemodynamic patterns have also been notedin individuals with diagnoses such as schizophrenia (Shinba et al., 2004; Suto,Fukada, Ito, Uehara, & Mikuni, 2004) and mood disorders (Matsuo, Kato, Fukuda,& Kato, 2000; Matsuo, Kato, & Kato, 2002) as compared to healthy controls. Pre-vious fMRI, PET, and SPECT studies have commonly found reductions or altera-tions in hemodynamic response with aging, neurological disease, and psychiatricdiagnoses (Mehagnoul-Schipper et al., 2002; Weinberger et al., 2001). Thereforethe findings of these studies are consistent, and suggest that as fNIRS techniquescontinue to be developed, the study of various population groups using this methodwill be beneficial.

fNIRS AND REHABILITATION

While limited fNIRS studies have been conducted within the rehabilitationpopulation, we argue that this is an area where this technology may be most appli-cable. As the focus of rehabilitation is on increasing functional capacity throughtherapeutic interventions, it seems possible that Obrig and Villringer’s (2003) callfor additional studies of basic paradigms with cortical regions that have been welldefined, such as primary and secondary sensory areas, may be addressed readilywithin this population. In addition, the opportunity to compare healthy controlswith those who have acquired brain injury may actually aid in clarifying what hasbeen found regarding the hemodynamics associated with cortical functioning forboth basic paradigms, as well as more complex cognitive processes, such as languageand memory. It seems possible that the more basic components of functions, whichcould be duplicated in fMRI paradigms where movement is limited, could beassessed using both fMRI and fNIRS for comparison, after which studies couldbe extended to examine actual functional activities, and could be compared to thebasic information acquired through both imaging methods. Consider the study byMiyai and colleagues, which was described earlier in this paper: In this study, sub-jects engaged in active walking, foot movements only, arm swing only, and motorimaging. Although basic localization of motor functioning has been establishedusing other techniques, because movement in this study was broken down and couldbe studied actively using fNIRS, the results of this study provided new informationabout the cortical mapping of various components of gait activity. In addition, fNIRSallowed for the study of actual gait, which is not possible using fMRI. By designingthe study to include the assessment of some gait components using both fMRI andfNIRS, similar activation patterns could be observed, helping to validate the findings.Based on their findings suggesting that it is possible to map dynamic activities, such asgait, using fNIRS, the authors suggest that this technique may be useful in evaluating


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pathological gait and as part of rehabilitative therapy. This study presents a designthat is ideally suited to study functional activity in rehabilitation, and which wouldnot be possible utilizing other neuroimaging techniques alone.

In yet another study that speaks to the need to assess dynamic activities withmethods that allow for performance of actual functional tasks, Okamoto and collea-gues (2004) found significant differences in areas of cortical activation when subjectsperformed an actual functional task (apple peeling) during fNIRS, and when thesame task was performed in a mock fashion during simultaneous fMRI and fNIRS(actual apple peeling caused activation of the prefrontal cortex, while mock applepeeling did not). The authors argued that studying tasks in a simplified manner,as may be required by fMRI and similar neuroimaging methods, may not providean accurate picture of cortical activation that occurs during actual activities. Wewould argue that the ability to map activation accurately during activity has thepotential to greatly enhance our knowledge of healthy function, but also to learnhow about the correlations between the restoration of function and altered hemody-namic patterns following injury or during rehabilitation. Ultimately, increased accu-racy in brain mapping during rehabilitation has the potential to allow us to watchchanges in hemodynamics as function returns and design treatments to optimizerecovery.

To date there have been only a few studies reported in the literature actuallyutilizing fNIRS within neurorehabilitation populations, with most of these studiesbeing conducted with individuals who experienced stroke. Of the published studiesin this area, the majority have primarily focused on fNIRS measurements recordedduring motor exercises. The following sections review the literature available in theseareas and point to the need for further application of fNIRS technology for the studyof individuals in rehabilitation.

Stroke

In 2002, Miyai and colleagues assessed 6 nonambulatory patients with severehemiplegia following stroke. Study of these patients was conducted at 3 monthsfollowing stroke, on average. An fNIRS imaging system was implemented duringa treadmill-walking task under partial body weight support. Support was providedeither with mechanical assistance in swinging the paretic leg, or through use of atechnique provided by physical therapists that enhanced swinging of the pareticleg. Performance of the gait activity was associated with increases in oxy-Hb inthe medial primary sensorimotor cortex, with greater increases noted in the unaf-fected hemisphere, as compared to the affected hemisphere. Data indicated that,during hemiplegic gait, there was enhancement of premotor activation in the affec-ted hemisphere, and activation of the presupplementary motor area was alsonoted. The facilitation technique provided by the physical therapist was shownto induce increased cortical activations as well as gait performance, as comparedto the use of mechanical assistance. The authors concluded that multiple motorareas, including the premotor cortex (PMC) and presupplementary motor area(PSMA) might be involved in the restoration of gait function in patients withsevere stroke.


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In an additional study, Mayai and colleagues (Mayai, Yagura, Hatakenaka,Oda, Konishi, & Kubota, 2003) conducted an fNIRS gait study of eight patientswith stroke. Cortical activities were measured during hemiparetic gait activities ona treadmill both before and after 2 months of inpatient rehabilitation. They foundinitial asymmetries in activation in the medial primary sensory cortex (SMC), pre-motor cortex, and supplementary motor area (SMA), with increased oxygenatedhemoglobin levels in the unaffected hemisphere, as compared to the affectedhemisphere, during gait activities. Improvement in assymetrical SMC activation cor-related with improvement on gait tasks. They concluded that recovery of locomotionafter stroke may be associated with improved asymmetry in SMC activation andenhanced premotor cortex activation in the affected hemisphere.

Another study of stroke patients (Kato et al., 2002) compared fNIRS andFMRI to examine six patients who experienced stroke, specifically within the distri-bution of the middle cerebral artery (MCA), exhibited left hemiparesis, and recov-ered to the point that they had minimal or mild residual hemiparesis. Subjectswere studied during a hand movement task of both the unaffected and affected hand.Results of both fMRI and fNIRS studies found evidence suggesting that compen-sation or reorganization of the hemisphere ipsilateral to the affected hand may con-tribute to recovery from hemiparesis. The authors concluded that fNIRS was usefulfor the study of poststroke alterations in motor functioning.

In 1998, Sakatani and colleagues conducted a study of cerebral blood oxygen-ation and hemodynamic response differences in the left prefrontal cortex of 29 sub-jects engaged in a confrontational naming task. The sample consisted of 10 post-stroke nonfluent (Broca’s) aphasia patients, 6 post-stroke non-aphasic patients,and 13 age-matched healthy controls. Results indicated differences between theaphasic and non-aphasic groups in patterns of change in the fNIRS parametersinduced by the language tasks, although results within groups were variable. Forexample, in both the healthy control group and the nonaphasic stroke patients, oxy-gen metabolism and hemodynamics of the left prefrontal cortex changed signifi-cantly with performance of the language task. The most common pattern ofchange noted for both of these groups was an increase in oxy-Hb and total-Hb witha slight decrease or no change in deoxy-Hb, with some within group variations ofthis pattern noted. In contrast, for the aphasic group who had some difficulty in per-forming the language task, the most common pattern observed was an increase indeoxy-Hb with an increase of oxy-Hb and total-Hb. Statistical analysis demon-strated a significant difference in deoxy-Hb between the aphasic and non-aphasicgroups, with no significant differences found between the healthy controls andnon-aphasic stroke subject groups. The authors asserted that the significantly differ-ent pattern observed in the aphasic group as they engaged in language tasks sug-gested that the left prefrontal cortex of aphasic patients utilized more oxygenduring such tasks as compared to nonaphasics. The multiple activation patternsobserved within groups suggested some individual differences in activation associa-ted with the performance of language-based tasks.

Saitou, Yanagi, Hara, Tsuchiya and Tomura (2000) conducted a study of 44post-stroke patients with hemiplegia and 24 healthy controls. They asked subjectsto perform several physical and occupational therapy related tasks. Healthy controlsubjects performed a head up tilt (HUT) task, as well as calculations and an erg-


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ometer task. Stroke patients performed these same tasks as well as tasks involvingreading aloud, listening to music, reciprocal extension, non-paralyzed extension,passive range of motion, pulley, bridge, facilitation, stand-up, and gait activities.Changes in cerebral blood volume (CBV) and cerebral oxygen volume (COV) weremeasured with an fNIRS apparatus placed at mid-forehead in healthy controls andover the impaired cerebral hemisphere among hemiplegic patients. In healthy con-trols, results indicated that the change patterns of CBV and COV differed betweentasks: A decrease in COV was noted with HUT, a limited increase in both COVand CBV was observed with the calculation task, and a gradual increase in bothmeasures was noted with ergometer tasks. In hemiplegic patients, results indicatedsignificant (positive) CBV changes with performance of ergometer, facilitation,stand-up, and gait tasks. Significant (negative) changes were noted with use of apassive movement device to produce finger extension. Significant (positive) changesin COV were noted in ergometer and facilitation tasks, and (negative) in HUT. Theauthors concluded that fNIRS was useful for observing changes in hemodynamicsand oxygenation in various types of rehabilitation interventions. It was also notedthat some tasks increased both COV and CBV (ergometer and facilitation) in theaffected prefrontal cortex of hemiplegic patients.

Murata, Sakatani, Katayama, and Fukaya (2002) used fNIRS to observe con-centration changes of deoxy-Hb, oxy-Hb, and Total-Hb in a group of six patientswith cerebral ischemia as compared to six healthy controls. FNIRS results were com-pared with BOLD-fMRI findings. Their results indicated differences in cerebralblood oxygenation between the two groups during performance of a hand-graspingtask, which at the behavioral level all patients could perform in a manner similar tocontrols. Specifically, within the control group, decreases in deoxy-Hb and associa-ted increases in oxy-Hb and total-Hb in the primary sensory cortex were observedduring the task performance. In comparison, the patient group results indicated asignificant deoxy-Hb increase from baseline, as well as an increase in oxy-Hb andtotal-Hb, indicating cerebral blood flow increases in response to neuronal activity.In comparison to the fNIRS findings, BOLD-fMRI findings indicated only limitedactivation areas in the affected primarily sensorimotor cortex of patients. Theauthors suggest that BOLD-fMRI may overlook activation areas unless bothincreases and decreases of signal are taken into consideration.

In another comparison study of fMRI and fNIRS (Kato, Izumiyama,Koizumi, Takahashi, & Itoyama, 2002), six right-handed patients who sufferedMCA territory cerebral infarction with minimal or mild residual left hemiparesiswere evaluated. The focus was on evaluation of compensatory motor activation ofcortical regions using fMRI and fNIRS during a hand movement task at chronicstages. Five healthy controls were also examined. Activation patterns between fMRIand fNIRS were consistent, however it was noted that fNIRS detected only super-ficial activation. In addition it was reported that while fMRI had superior spatial res-olution, fNIRS provided a dynamic profile of activation. fMRI and fNIRSactivation patterns of healthy controls during each hand movement were notedpredominantly in the contralateral primary sensorimotor cortex and supplementarymotor areas. Stroke patients exhibited this same pattern with movement of the unaf-fected hand. With movement of the affected hand, however, the activation patternsof stroke patients revealed extended activation in the contralateral motor cortex, as


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well as in the primary motor cortex and supplementary motor areas of the ipsilateralmotor cortex. The authors suggested that the fMRI and fNIRS findings of this studyprovided evidence that compensation or reorganization of the ipsilateral motor cor-tex contributes to the recovery from poststroke hemiparesis. As a result, the authorsconcluded that fNIRS might be a useful tool for studying cerebral reorganizationfollowing stroke.

Overall, most of these studies involved evaluation of motor functioning. Thoseusing direct comparison to fMRI, found consistent activation patterns. In studieswhere more complex cognitive processes were included, results were somewhat morevariable, which is consistent with the previous discussion of the literature. Taken as awhole these studies demonstrate the usefulness of fNIRS for evaluating hemody-namic patterns associated with active function following stroke.

Traumatic Brain Injury

The current authors are aware of no published studies directly evaluating the useof fNIRS with traumatic brain injury (TBI) patients during the course of rehabili-tation. fNIRS studies involving individuals with TBI have generally examinedpatients in acute care, particularly in intensive care units. For example, Gopinathand colleagues (Gopinath, Robertson, Grossman, & Chance, 1993) applied fNIRSto detect the presence of intracranial hematoma in 46 patients with head injury. Ofthe 40 patients with intracranial hematomas identified by CT, fNIRS demonstratedgreater absorption of light on the side of the hematoma in all 40 cases. fNIRS wasthen used to follow up patients post-operatively in the ICU where differences inoptical density of tissue on the injured versus non-injured hemispheres were mea-sured. In 36 of the 40 patients with hematoma, the previously observed asymmetryresolved following surgical evacuation, or after natural reabsorption of the hema-toma. In four patients who developed delayed or postoperative hematomas, asym-metry (as demonstrated with fNIRS) persisted. The authors concluded that fNIRSwas a useful tool for this type of assessment in head-injured patients.

Robertson, Gopinath, and Chance (1995) first applied fNIRS serially over thecourse of 3 days in the detection of delayed intracranial hematomas in 167 patientswith head injury. They concluded that early diagnosis using fNIRS might reducesecondary injury by allowing for early identification and treatment of delayed hema-tomas. In another study, Kirkpatrick and colleagues (Kirkpatrick, Smeilewski,Czosnyka, Menon, & Pickard, 1996) assessed the potential use of fNIRS in a neuroin-tensive care unit with 14 ventilated patients with head injury. They used a multimod-ality recording system and recorded fNIRS-derived changes in oxy-Hb and deoxy-Hb,as well as signals derived from intracranial pressure, cerebral perfusion pressure, per-ipheral oxygen saturation, and jugular venous saturation. Evaluation of the recordeddata indicated that fNIRS showed correlated changes in 97% of events recorded thatshowed clear changes in cerebral perfusion pressure accompanied by hemodynamicchanges in the middle cerebral artery flow velocity and cortical perfusion as measuredby other methods.

In another study of patients in intensive care, Kampfl and colleagues (Kampfl,Pfausler, Denchev, Jaring, & Schmutzard, 1997) used fNIRS to evaluate changes inregional cerebral oxygen saturation (rSO2) in eight patients with severe head injury.


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They assessed four patients with intracranial pressure (ICP) higher than 25 mmHg,and four with ICP lower than 25 mmHg. At baseline, they found fNIRS values tobe significantly higher in the low ICP group as compared to the high ICP group,despite the fact that other measures (i.e., arterial PO2, pCO2, peripheral oxygensaturation, and transcranial Doppler sonography) did not detect significant differ-ences between groups. Patients in both groups were then given 50% O2 for a periodof 3 minutes, followed by follow-up measurement. Again, similar values in periph-eral oxygen saturation, arterial PO2, and TCD velocities were found. Using fNIRS,however, rSO2 values were found to be significantly increased in the low ICP groupafter the hyperoxygenation period, but no detectable change was noted in the highICP group, and rSO2 values in the high ICP group were significantly lower thanin patients in the low ICP group. The authors suggested that fNIRS might be usefulas a monitoring tool for the non-invasive evaluation of impaired cerebral microcir-culation in head-injury patients who have increased ICP. In contrast, Buchner andcolleagues (Buchner, Meizensberger, Dings, & Roosen, 2000) monitored 31 patientswith severe brain injury during acute intensive care. fNIRS was compared withinvasive ICP, CCP, and regional brain tissue PO2 monitoring. They found a highfailure rate and limited sensitivity of fNIRS as compared to other measures, anddetermined the fNIRS is not suitable for clinical use for neuromonitoring followingbrain injury.

In a preliminary study of children who had experienced traumatic brain injury(Adelson, Nemoto, Colak, & Painter, 1998), fNIRS monitoring was used to continu-ously monitor 10 patients and was found to reliably detect changes in cerebral hemo-dynamics. The authors suggested that FNIRS may be a useful tool to gain animproved understanding of the diffuse cerebral swelling seen in children followingsevere TBI.

Brawanski, Faltermeier, Rothoerl, and Woertgen (2002) compared the mea-sure of local hemoglobin oxygen saturation (rSO2) by fNIRS and a slightly moreinvasive measure of local oxygen pressure in white matter of the brain (tipO2), toassess whether tipO2 and rSO2 signals provide similar information for monitoringpatients in neurosurgical intensive care units. A tipO2 probe and an fNIRS sensorwere positioned over the frontal lobe area of most significant injury (as indicatedby CT scan) in 12 patients, 9 with severe TBI and 3 with aneurismal subarachnoidhemorrhage. By means of fNIRS-derived spectral analysis, the authors determinedthat tipO2 and rSO2 signals contain similar information, despite the fact that differ-ent registration methodologies are used.

Despite the paucity of fNIRS studies of individuals with TBI to date, we wouldargue that, based on the available rehabilitation literature and the results of the workconducted with stroke patients, the development of paradigms to study those under-going rehabilitation following TBI is both appropriate and important. It seems likelythat designing studies to utilize fNIRS findings in conjunction with the serial neuro-imaging and neuropsychological testing protocols, which are often used to assessrecovery from injury, could be useful both to validate fNIRS techniques, and, ulti-mately, to provide data about functional recovery not possible with the currentlyused neuroimaging methods. We are currently conducting pilot studies utilizingfNIRS with this population and see the potential for growth in this area of studyin the future.


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fNIRS: ASSETS AND CONSIDERATIONS

In sum, the research to date has begun to examine numerous applicationsof fNIRS and has helped to establish some of the unique assets offered by thistechnology. Although most studies seem to generally conclude that fNIRS tech-nology is applicable to functional brain mapping, we have described some limitationsand needs for further development throughout this paper. Table 1 provides a sum-mary of some of the strengths and limitations that may be important to considerwhen designing and implementing fNIRS studies.

Regarding limitations: In evaluating the available literature, there are currentlydifferences in the reporting of oxy-Hb, deoxy-Hb, and total-Hb as parameters ofchoice for indicating cortical activation. Also, many of the studies in the literatureutilize different instrumentation with varied configurations, numbers, and place-ments of optodes. In addition, as previously mentioned, there is tremendous varia-bility in the types of tasks assessed, especially when looking at the literatureregarding higher-level cognitive functioning. Due to differences such as these, as wellas factors such as limited spatial resolution, differences in skull and hair thickness atvarious places on the head, and differences in statistical analysis, some difficulty indirect comparison between studies needs to be considered.

Table 1 Summary of pros and cons of fNIRS application to rehabilitation

Advantages

1. Portability . Instrumentation for system is typically

limited to a laptop and head unit

2. Availability . Low cost systems

. Is not dependent on permanent,

large-scale instrumentation

3. Non-invasive . Does not require intravenous

administration of radioisotopes

4. Allows observation

of ‘‘actual’’ not ‘‘mock’’

tasks performance

. Can be used to observe ‘‘real life’’ behaviors

. Eliminates need to use artificial or

imaginary tasks during brain imaging

5. Allows observation of

dynamic tasks performance

. Allows collection of real time data while

the individual is performing tasks (e.g., walking)

Disadvantages

1.Lack of standardized

fNIRS measurements

. Much variability in studies to date,

regarding what measurement (deoxy-hB, oxy-hB,

total Hb) is reported

2. Variability in instrumentation . Many systems have been independently

developed and subsequently may have

variability in capacity

3. Limited spatial resolution . While temporal resolution is strong,

spatial resolution is limited to

approximately 1 inch depth

4. Appropriateness . Need to establish further reliability

and validity of fNIRS measurement

. Need to establish which aspects of

rehabilitation may most benefit from fNIRS


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Despite limitations, however, we have argued that fNIRS has several advan-tages over other methods, especially for the study of functional activity: The size,cost, and portability are major advantages regarding the actual imaging equipment.The safety and non-invasiveness of the procedure provides improved patient comfortand convenience. Most importantly, the ability to collect data while individuals areengaged in everyday activities has the potential to provide more accurate dataregarding hemodynamic changes associated with functional activity.

FUTURE DIRECTIONS

The present array of imaging technologies provides researchers and, to a lesserdegree, clinicians with an arsenal of ways to measure changes in the brain. Yet it islikely that emerging technologies such as fNIRS will hold even greater promise forneurorehabilitation by bringing the imaging lab into the rehabilitation clinic. Obrigand Villringer (2003) suggest the need for further methodological and technicaldevelopments, further studies to define spatial resolution, and more standardizedstatistical=data analysis as some issues for the future development of fNIRS in orderto provide increased standardization and comparability within the literature. Basedin this review, the current authors are in agreement with this assessment. While it isunlikely that fNIRS will replace fMRI or other neuroimaging methods, it appearsthat, with development, it has the potential to provide superior data regarding func-tional activity in rehabilitation. While further reliability and validity may need to beestablished for more basic functions and then applied to more complex cognitivefunctions, a review of the literature suggests that the ability to do so is promising.Ultimately, this may allow for the development of more accurate and effective thera-peutic interventions and improved outcomes for individuals recovering from bothphysically and cognitively disabling illnesses or injuries.

ACKNOWLEDGMENT

Preparation of this manuscript was supported by grant number R03-HD043118-01 (PI: Ricker) from the National Institutes of Health.

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